The present invention relates to a controlled release formulation for administration of antidepressant drugs such as bupropion to a subject and to antidepressant formulations of improved stability.
Bupropion, or (xc2x1)-2-(tert-butylamino)3xe2x80x2-chloropropiophenone, is an aminoketone antidepressant. It may be administered in the form of a pharmaceutically acceptable salt, such as bupropion hydrochloride.
Bupropion is extensively metabolised in mammals and on oral administration, only a small portion of the administered dose reaches the systemic circulation intact. For example, the absolute bioavailability of bupropion in mammals such as rats and dogs ranges from 5% to 20%.
It would therefore be useful to employ a controlled release formulation of bupropion.
The stability of bupropion on storage has also been a cause for concern, the compound being subject to hydrolytic decomposition during storage (Ther. Drug Monit. (1985), v. 7(y), pp. 447-458; GA (1985), v. 101, pp. 210748e of UX; and J. Pharm. Sci. (1980), v. 69, pp. 1206-1209).
Similar problems of active metabolism and storage instability are encountered with many antidepressant drugs.
It is an object of the present invention to ode a controlled release pharmaceutical formulation containing as active ingredient an antidepressant such as bupropion or a pharmaceutically acceptable bupropion salt, whereby the active ingredient is released over a period of time to provide improved availability of the drug.
It is a further object of the invention to provide controlled release pharmaceutical formulations whereby the active ingredient is released in either a continuous or a pulsatile manner.
In accordance with one embodiment, the invention provides a controlled release pharmaceutical formulation which comprises an effective amount of bupropion hydrochloride and from about 1% to about 70% by weight of a polymer selected from the group consisting of a) at least one uncrosslinked polymer selected from the group consisting of hydroxyethyl cellulose, sodium carboxymethyl cellulose, hydroxypropyl cellulose and hydroxypropylmethyl cellulose; b) at least one crosslinked insoluble polymer; and c) a mixture of (a) and (b).
The formulations of the invention may further comprise a stabilising agent, such as a saturated polyglycolised glyceride. The polyglycolised glyceride may consist of mono-, di- and triglycerides and of mono- and di- fatty acid esters of polyethylene glycol.